Biomedical subjects

M Ogata

Publications and source records attributed to M Ogata.

At least 37 records · Page 2Linked to original sources

PubMed2001

Prevalence of A-to-G mutation at nucleotide 3243 of the mitochondrial tRNA(Leu(UUR)) gene in Japanese patients with diabetes mellitus and end stage renal disease.

The A-to-G mutation at nucleotide 3243 of the mitochondrial tRNA(Leu(UUR)) gene (mt.3243A>G) is associated with both diabetes mellitus and myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Recently, this mutation was found in three diabetic subjects with progressive kidney disease, suggesting that it may be a contributing factor in the development of kidney disease in patients with diabetes. The aim of this study was to evaluate the contribution of this mutation to the development of end stage renal disease (ESRD) in patients with diabetes. The study group consisted of 135 patients with diabetes and ESRD. The control group consisted of 92 non-diabetic subjects with ESRD who were receiving hemodialysis. The mt.3243A>G mutation was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). We found the mt.3243A>G mutation in eight patients (8/135; 5.9%), all of whom were initially diagnosed with type II diabetes. Five of the eight patients were subsequently also diagnosed with MELAS. We did not find the mutation in any of the 92 nondiabetic subjects with ESRD. The prevalence of this mutation was 6.5-fold higher in patients with diabetes and ESRD than in those with diabetes alone (8/135 vs 5/550, respectively; chi2 = 13.704; P = 0.0002). The mt.3243A>G mutation may be a contributing genetic factor in the development of ESRD in Japanese patients with diabetes.

Adult↗

PubMed2001

Involvement of SHP-1 tyrosine phosphatase in TCR-mediated signaling pathways in lipid rafts.

To elucidate the process of TCR-mediated signaling pathways in lipid rafts, we constructed a chimeric molecule that localizes activated SHP-1 to rafts. Raft targeting of activated SHP-1 in Jurkat-derived transfectants completely inhibited the expression of CD69 and transcriptional factors after TCR cross-linking. Whereas the inducible tyrosine phosphorylation of TCR zeta and ZAP-70 and the kinase activity of Lck were intact, phosphorylated LAT was rapidly dephosphorylated by raft targeting of activated SHP-1, leading to defects in LAT activation and subsequent downstream signaling events. Intriguingly, recruitment of endogenous SHP-1 to rafts and its association with LAT were dramatically increased after TCR engagement, suggesting that SHP-1 is involved in raft-mediated T cell activation.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Lignans as anti-tumor-promoter from the seeds of Hernandia ovigera.

Seven lignans (2-8) isolated from the seeds of Hernandia ovigera L. (Hernandiaceae) were tested for their inhibitory effects on Epstein-Barr virus early antigen activation induced by 12-O-tetradecanoylphorbol 13-acetate in Raji cells. Using a primary screening test, all the lignans showed inhibitory activity with IC50 470-590 mol ratio/32 pmol TPA. The data demonstrated that these lignans might be valuable anti-tumor-promoters.

Anticarcinogenic Agents↗

PubMed2001

Protective effects of fluvastatin against reactive oxygen species induced DNA damage and mutagenesis.

Oxidative stress may be an important factor in the development of diabetic complications. Advanced glycation end-products have drown attention as potential sources of oxidative stress in diabetes. We investigated the protective effects of fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on oxidative DNA damage from reactive oxygen species or advanced glycation end-products in vitro, as well as effects of main fluvastatin metabolites and other inhibitors of the same enzyme, pravastatin and simvastatin. Protective effects were assessed in terms of the DNA breakage rate in a single-stranded phage DNA system in vitro. DNA was exposed to either reactive oxygen species or advanced glycation end-products. Fluvastatin and its metabolites showed a strong protective effect comparable to those seen with thiourea and mannitol, though pravastatin and simvastatin did not exert clear protective effects. Furthermore, fluvastatin reduced the mutagenesis by reactive oxygen species or advanced glycation end-products in Salmonella typhimurium test strains. Both pravastatin and simvastatin still lacked protective activity. Fluvastatin and its metabolites protect against oxidative DNA damage and may reduce risk of consequent diabetic complications.

Bacteriophages↗

PubMed2001

Surgical stress induces endotoxin hyporesponsiveness and an early decrease of monocyte mCD14 and HLA-DR expression during surgery.

UNLABELLED: It is generally accepted that major surgery is associated with severe alterations of the host-defense mechanisms. We investigated the effect of surgical stress on the immune system. Specifically, we studied the relationship between perioperative lipopolysaccharide (LPS) hyporesponsiveness and monocyte human leukocyte antigen-DR (HLA-DR) and CD14 expression during the perioperative period in 20 patients who underwent partial gastrectomy. This study demonstrated that surgical stress rapidly depressed monocyte mCD14 and HLA-DR expression in comparison with preanesthesia levels. Monocyte mCD14 expression recovered to preoperative levels on the first postoperative day, and monocyte HLA-DR expression recovered by the seventh postoperative day. Consistent with our previous study, LPS-induced tumor necrosis factor (TNF)-alpha production ex vivo was significantly suppressed from the beginning of the operation. On the contrary, the plasma interleukin-10 concentration started to increase after the surgical incision was made. LPS hyporesponsiveness was least at the end of the operation and returned to preoperative levels on the first postoperative day. In conclusion, the present study demonstrated that LPS responsiveness, plasma interleukin-10 concentration, and monocytes mCD14 and HLA-DR expression altered from the early period of surgery. These alterations may be related to the impairment of the immune system during the perioperative period. IMPLICATIONS: Recent studies demonstrate that surgical stress induces immune dysfunction. We found that surgical stress rapidly decreased monocyte mCD14 and human leukocyte antigen-DR expression, and endotoxin responsiveness. These findings suggest that early changes of the immune system caused by surgical stress contribute to postoperative complications such as sepsis and multiple organ failure.

Gastrectomy↗

PubMed2001

KB-R7943, a selective Na+/Ca2+ exchange inhibitor, protects against ischemic acute renal failure in mice by inhibiting renal endothelin-1 overproduction.

We investigated whether the preischemic or postischemic treatment with KB-R7943, a novel and selective Na+/Ca2+ exchange inhibitor, has renal protective effects in mice with ischemic acute renal failure (ARF). Ischemic ARF was induced by clamping the left renal pedicle for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal function was markedly diminished 24 h after reperfusion. Preischemic treatment with KB-R7943 attenuated the ARF-induced renal dysfunction. The ischemia/reperfusion-induced renal dysfunction was also overcome by postischemic treatment with KB-R7943. Histopathologic examination of the kidneys of ARF mice revealed severe renal damage such as tubular necrosis, proteinaceous casts in tubuli, and medullary congestion. Histologically evident damage and Ca2+ deposition in necrotic tubular epithelium were improved by preischemic treatment with KB-R7943. In addition, preischemic treatment with KB-R7943 significantly suppressed the increment of endothelin-1 (ET-1) content in the kidney at 2, 6, and 24 h after reperfusion. These findings suggest that Ca2+ overload via the reverse mode of Na+/Ca2+ exchange, followed by renal ET-1 overproduction, plays an important role in the pathogenesis of the ischemia/reperfusion-induced ARF. KB-R7943 may prove to be an effective therapeutic agent for cases of ischemic ARF in humans.

Acute Kidney Injury↗

PubMed2001

Chlorophyll derived from Chlorella inhibits dioxin absorption from the gastrointestinal tract and accelerates dioxin excretion in rats.

We investigated the effects of chlorophyll derived from Chlorella on gastrointestinal absorption of seven types of polychlorinated dibenzo-p-dioxin (PCDD) and 10 types of polychlorinated dibenzofuran (PCDF) in Wistar rats. Twenty-eight rats were randomly distributed into seven groups (n = 4). After overnight food deprivation, rats were given 4 g of the basal diet or 4 g of the chlorophyll diet containing 0.01-0.5% chlorophyll one time on day 1; each diet also contained 0.2 mL PCDD and PCDF standard solutions. The amounts of fecal excretion of PCDD and PCDF congeners from days 1 to 5 in the group fed 0.01% chlorophyll were 64.8% for 1,2,3,7,8-pentaCDD, 78.6% for 1,2,3,4,7,8-hexaCDD, 73.5% for 1,2,3,6,7,8-hexaCDD, 58.5% for 1,2,3,7,8,9-hexaCDD, 33.3% for 1,2,3,4,6,7,8-heptaCDD, 85.7% for 1,2,3,7,8-pentaCDF, 77.3% for 2,3,4,7,8-pentaCDF, 88.6% for 1,2,3,4,7,8-hexaCDF, 78.0% for 1,2,3,6,7,8-hexaCDF, 62.5% for 1,2,3,7,8,9-hexaCDF, 84.1% for 2,3,4,6,7,8-hexaCDF, 41.7% for 1,2,3,4,6,7,8-heptaCDF, and 40.0% for 1,2,3,4,6,7,8-heptaCDF greater (p < 0.01) than those of the control group, respectively. The fecal excretion of PCDD and PCDF congeners was remarkably increased along with the increasing dietary chlorophyll. The amounts of PCDD and PCDF congeners in rats on day 5 administered dioxin mixtures were lower in the 0.01% chlorophyll group than in the control group, ranging from 3.5 to 50.0% for PCDD congeners and from 3.7 to 41.7% lower for PCDF congeners, except for 2,3,7,8-tetrachlorodibenzofuran. The amount of PCDD and PCDF congeners in rats was remarkably decreased along with the increasing dietary chlorophyll. These findings suggest that chlorophyll is effective for preventing dioxin absorption via foods.

Animals↗

PubMed2001

Mutations in the coding region of the neurogenin 3 gene (NEUROG3) are not a common cause of maturity-onset diabetes of the young in Japanese subjects.

Mutations in transcription factors that play a role in the development of the endocrine pancreas, such as insulin promoter factor-1 and NeuroD1/BETA2, have been associated with diabetes. Cell type-specific members of the basic helix-loop-helix (bHLH) family of transcription factors play essential roles in the development and maintenance of many differentiated cell types, including pancreatic beta-cells. Neurogenin 3 is a bHLH transcription factor that is expressed in the developing central nervous system and the embryonic pancreas. Mice lacking this transcription factor fail to develop any islet endocrine cells and die postnatally from diabetes. Because neurogenin 3 is required for the development of beta-cells and other pancreatic islet cell types, we considered it a candidate diabetes gene. We screened the coding region of the human neurogenin 3 gene (NEUROG3) for mutations in a group of unrelated Japanese subjects with maturity-onset diabetes of the young (MODY). We found three sequence variants: a deletion of 2-bp in the 5'-untranslated region (NEUROG3-g.-44-45delCA), a G-to-A substitution in codon 167 (g.499G/ A), resulting in a Gly-to-Arg replacement (G/R167), and a T-to-C substitution in codon 199 (g.596T/C), resulting in a Phe/Ser polymorphism F/S199. These polymorphisms were not associated with MODY, thereby suggesting that mutations in NEUROG3 are not a common cause of MODY in Japanese patients.

Amino Acid Substitution↗

PubMed2001

Pre- or post-ischemic treatment with a novel Na+/Ca2+ exchange inhibitor, KB-R7943, shows renal protective effects in rats with ischemic acute renal failure.

We investigated the effects of pre- or post-ischemic treatment with KB-R7943, a new Na+/Ca2+ exchange inhibitor, on ischemic acute renal failure (ARF) in rats, and these were compared with the effects of verapamil. Ischemic ARF was induced by clamping the left renal pedicle for 45-min followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal function markedly decreased 24 h after reperfusion. Pre-ischemic treatment with KB-R7943 or verapamil attenuated the ARF-induced renal dysfunction. The ischemia/reperfusion-induced renal dysfunction was overcome by post-ischemic treatment with KB-R7943 but not with verapamil. Histopathological examination of the kidney of ARF rats revealed severe renal damage, and suppression of the damage was seen with post-ischemic treatment with KB-R7943. KB-R7943 markedly suppressed the increment of endothelin-1 (ET-1) content in the kidney at 2, 6, and 24 h after reperfusion. No significant changes in Na+/Ca2+ exchanger protein expression in renal tissue were observed with 45-min ischemia, 6 h after reperfusion and KB-R7943 treatment. These results suggest that Ca2+ overload via the reverse mode of Na+/Ca2+ exchange, followed by ET-1 overproduction, seems to play an important role in the pathogenesis of the ischemia/reperfusion-induced ARF. KB-R7943, which is effective in both cases of pre- and post-ischemic treatments, may prove to be an effective therapeutic agent for cases of ischemic ARF.

Acute Kidney Injury↗

PubMed2001

[Development of three-dimensional stereo viewer for high-resolution data].

In order to visualize high-resolution three-dimensional (3D) data as a stereogram, a real-time volume-rendering system using a hardware graphic board and conventional PC was developed. A 256(3) data set could be visualized at a redrawing rate of 12 Hz, and a 512(3) data set at a rate of 2.5 Hz. It was demonstrated that stereogram visualization using volume graphic hardware architecture potentially enables rapid examination of high-resolution 3D data by changing visualization parameters such as level, window, transfer function for opacity, and color map or coordinate direction.

Computer Graphics↗

PubMed2001

[Relationship between glycoxidation and cytokines in the vitreous of eyes with diabetic retinopathy].

PURPOSE: To investigate the correlations among pentosidine, an advanced glycation end product, and related cytokines [vascular endothelial growth factor(VEGF), transforming growth factor(TGF)-beta 2, and monocyte chemotactic protein(MCP)-1], and active oxygen in the vitreous of patients with diabetic retinopathy(DR). METHODS: Vitreous samples from 43 eyes undergoing vitrectomy to treat DR were divided into four subgroups and analyzed. Vitreous samples from 21 eyes of patients with no systemic conditions were age- and sex-matched controls. The vitreous levels of pentosidine, cytokines, and hydrogen peroxide (H2O2) were determined by high performance liquid chromatography, enzyme-linked immunosorbent assay, and titanium-hydrogen peroxide colorimetric method respectively. RESULTS: The levels of pentosidine, VEGF, total TGF-beta 2, and MCP-1 in the vitreous samples of eyes with DR were significantly higher than in the controls(p < 0.01). Significant correlation(p < 0.01) was found between pentosidine and VEGF, pentosidine and H2O2, H2O2 and VEGF, and total TGF-beta 2 and MCP-1(r = 0.62, 0.58, 0.65, and 0.59, respectively). CONCLUSIONS: These results suggest that the elevated levels of the glycoxidation product pentosidine may have caused increased levels of VEGF in the vitreous of DR patients. Increased levels of total TGF-beta 2 and MCP-1 together may also play an important role in the development of DR.

Arginine↗

PubMed2001

[Prognostic factors of renal pelvic and ureteral cancer: a multivariate analysis].

We clinicopathologically reviewed 54 cases (40 males and 14 females) of renal pelvic and ureteral cancer examined between 1983 and 1998, in order to determine the impact of prognostic factors. Follow-up ranged from 2 to 173 months (mean, 45.6 months). The age of the patients ranged from 39 to 88 years (mean, 68.9 years). The 1, 3 and 5-year cause-specific survival rates (Kaplan-Meier's method) for all of the patients were 74.6%, 58.4% and 54.5%, respectively. According to univariate analysis, a high grade and high stage of tumor, the presence of lymphatic invasion and positive regional lymph nodes indicated a significantly poor prognosis. On the other hand, multivariate analysis using Cox proportional hazards regression revealed the presence of lymphatic invasion as the most significant predictor of survival. Therefore, patients with lymphatic invasion have a poor prognosis, and the development of effective adjuvant therapy is needed to improve the outcome in these patients.

Adult↗

PubMed2001

Factors determining outcome in elderly patients with severe COPD on long-term domiciliary oxygen therapy.

The objective of the present study was to identify factors that determine outcome in elderly patients receiving long term domiciliary oxygen therapy (LTOT) for chronic obstructive pulmonary disease (COPD). One hundred fifty-seven COPD patients (121 male, 36 female) receiving LTOT were followed-up from 1983 to 1994. Univariate and multivariate analysis by Cox's proportional hazards ratio model and Kaplan-Meier survival estimates were used to quantify the relationship among a total of 34 baseline variables and overall mortality. By December 31, 1995, 96 patients (61.2%) had died and 13 (8.3%) were unavailable for follow up. Mean age of the patients was 79.2 yrs and mean duration of LTOT was 2.81 yrs. The mean FEV1 was 0.80 L and mean FEV1/FVC was 48%. The overall survival was poor and 5-yr survival was 21.6% (median survival: 3.01 yrs). Among the variables tested by univariate analysis, factors associated with poor outcome were as follows: %IBW < or = 85 (HR = 2.15, p < 0.001), serum albumin (g/dl) < or = 3.5 (1.81, p < 0.01), hemoglobin (g/dl) < or = 11.0 (1.86, p < 0.01), FEV1/FVC > 50% (0.63, p < 0.05), and high dyspnea ranking (grade 4 or 5) (1.74, p < 0.05). The coexistence of bronchiectasis (3.96, p < 0.01) and malignancy (1.85, p < 0.01) also contributed to poor outcome. Multivariate analysis showed that independent prognostic factors influencing outcome included: nutritional status (%IBW) (HR = 2.08, p < 0.01), dyspnea ranking (2.04, p < 0.01), coexistence of malignancy (2.02, p < 0.01), and FEV1/FVC (0.52, p < 0.01). We conclude that the outcome in elderly COPD patients receiving LTOT is poor, and that outcome is independently influenced by four major factors: malnutrition, severity of dyspnea, coexistence of malignancy, and airflow obstruction.

Aged↗

PubMed2001

[Lymphedema after radical prostatectomy: a case report].

We report a case of intractable lymphedema of the left leg following radical prostatectomy. The 69-year-old male patient complained of difficulty walking, caused by severe lymphedema. Intraarterial autologous lymphocyte transfusion therapy was performed because of failure of conventional conservative therapy, and the leg edema resolved almost completely. However, the treatment did not improve the penoscrotal edema necessitating excision of the edema and skin graft in a separate procedure. The post-operative course was excellent and the patient's performance status improved to 1 from 3.

Aged↗

PubMed2001

[Hepatic infusion of docetaxel using PEIT for a patient with stage IV breast cancer].

Hepatic infusion of docetaxel using PEIT was performed for a patient with stage IV breast cancer. Docetaxel was effective to a solitary liver metastatic lesion. A 64-year-old woman was admitted to our hospital because of a left breast mass that was bleeding. She was diagnosed with stage IV breast cancer. Surgery was performed on February 16th. The pathological diagnosis was invasive ductal carcinoma, and hormone receptors were negative. Two weeks after operation, monthly docetaxel injections were given together with doxifluidine 400 mg/day p.o., cyclophosphamide 50 mg/day p.o., and fadrozole hydrochloride hydrate 2 mg/day p.o. After two courses, hepatic infusion of docetaxel was performed using PEIT after informed consent. The patient's high serum CEA and CA15-3 level returned to the normal range. A metastatic lesion on CT changed to a cystic pattern. These results suggest that PEIT is worth trying in patients with solitary liver metastasis from breast cancer.

Antineoplastic Agents, Phytogenic↗

PubMed2000

Spin-triplet superconductivity due to antiferromagnetic spin-fluctuation in Sr2RuO4

A mechanism leading to the spin-triplet superconductivity is proposed based on the antiferromagnetic spin-fluctuation. The effects of anisotropy in spin-fluctuation on the Cooper pairing and on the direction of d vector are examined in the one-band Hubbard model with random-phase approximation. The gap equations for the anisotropic case are derived and applied to Sr2RuO4. It is found that a nesting property of the Fermi surface together with the anisotropy leads to the triplet superconductivity with the d = &zcirc;(sink(x)+/-isink(y)), which is consistent with experiments.

Journal Article↗

PubMed2000

Spontaneous deformation of the fermi surface due to strong correlation in the two-dimensional t- J model

The Fermi surface of the two-dimensional t- J model is studied using the variational Monte Carlo method. We study the Gutzwiller-projected d-wave superconducting state with an additional variational parameter t(')(v) corresponding to the next-nearest-neighbor hopping term. It is found that the finite t(')(v)<0 gives the lowest variational energy in the wide range of hole-doping rates. The obtained momentum distribution function shows that the Fermi surface deforms spontaneously. It is also shown that the Van Hove singularity is always located very close to the Fermi energy. Using the Gutzwiller approximation, we show that this deformation is due to the Gutzwiller projection operator or the strong correlation.

Journal Article↗

PubMed2000

Serine 6 of Lck tyrosine kinase: a critical site for Lck myristoylation, membrane localization, and function in T lymphocytes.

Lck is a member of the Src family kinases expressed predominantly in T cells, and plays a pivotal role in TCR-mediated signal transduction. Myristoylation of glysine 2 in the N-terminal Src homology 4 (SH4) domain of Lck is essential for membrane localization and function. In this study, we examined a site within the SH4 domain of Lck regulating myristoylation, membrane localization, and function of Lck. A Lck mutant in which serine 6 (Ser6) was substituted by an alanine was almost completely cytosolic in COS-7 cells, and this change of localization was associated with a drastic inhibition of myristoylation in this mutant. To assess the role of Ser6 of Lck in T cell function, we established stable transfectants expressing various Lck mutants using Lck-negative JCaM1 cells. The Lck mutant of Ser6 to alanine, most of which did not target to the plasma membrane, was not able to reconstitute TCR-mediated signaling events in JCaM1 cells, as analyzed by tyrosine phosphorylation of intracellular proteins and CD69 expression. These results demonstrate that Ser6 is a critical factor for Lck myristoylation, membrane localization, and function in T cells, presumably because the residue is important for N-myristoyl transferase recognition.

Alanine↗